Lateral flow assay (LFA) has been a valuable diagnostic tool in many important fields where rapid, simple, and on-site detection is required, for applications such as pregnancy tests and infectious disease prevention. Currently, two types of LFAs are available lateral flow immunoassay (LFIA) and nucleic acid lateral flow assay (NALFA). Both are generally used for the testing of proteins and nucleic acids. However, enzyme activities and small molecules without the corresponding binding partner cannot be detected by the existing LFAs. In this paper, we introduce a LFA approach termed affinity-switchable lateral flow assay (ASLFA) to overcome the limitations. The detection principle is based on the switchable binding between the affinity-switchable biotin (ASB) probe and avidin protein. In the presence of the target molecule, the activated ASB probe would be captured by the avidin, thereby leaving a distinct test line on the membrane. The ASLFA concept was demonstrated by testing the F ion, NADH cofactor, and nitroreductase activity. Thus, this general ASLFA can be used for the rapid detection of molecules that cannot be accessed by the classical LFAs.Levulinic acid is a versatile platform molecule with potential to be used as an intermediate in the synthesis of many value-added products used across different industries, from cosmetics to fuels. Thus far, microbial biosynthetic pathways having levulinic acid as a product or an intermediate are not known, which restrains the development and optimization of a microbe-based process envisaging the sustainable bioproduction of this chemical. One of the doors opened by synthetic biology in the design of microbial systems is the implementation of new-to-nature pathways, that is, the assembly of combinations of enzymes not observed in vivo, where the enzymes can use not only their native substrates but also non-native ones, creating synthetic steps that enable the production of novel compounds. Resorting to a combined approach involving complementary computational tools and extensive manual curation, in this work, we provide a thorough prospect of candidate biosynthetic pathways that can be assembled for the production of levulinic acid in Escherichia coli or Saccharomyces cerevisiae. Out of the hundreds of combinations screened, five pathways were selected as best candidates on the basis of the availability of substrates and of candidate enzymes to catalyze the synthetic steps (that is, those steps that involve conversions not previously described). Genome-scale metabolic modeling was used to assess the performance of these pathways in the two selected hosts and to anticipate possible bottlenecks. Not only does the herein described approach offer a platform for the future implementation of the microbial production of levulinic acid but also it provides an organized research strategy that can be used as a framework for the implementation of other new-to-nature biosynthetic pathways for the production of value-added chemicals, thus fostering the emerging field of synthetic industrial microbiotechnology.Screening molecular libraries for ligands capable of binding proteins is widely used for hit identification in the early drug discovery process. Oligonucleotide libraries provide a very high diversity of compounds, while the combination of the polymerase chain reaction and DNA sequencing allow the identification of ligands in low copy numbers selected from such libraries. Ligand selection from oligonucleotide libraries requires mixing the library with the target followed by the physical separation of the ligand-target complexes from the unbound library. https://www.selleckchem.com/ Cumulatively, the low abundance of ligands in the library and the low efficiency of available separation methods necessitate multiple consecutive rounds of partitioning. Multiple rounds of inefficient partitioning make the selection process ineffective and prone to failures. There are continuing efforts to develop a separation method capable of reliably generating a pure pool of ligands in a single round of partitioning; however, none of the proposed methods f umbrella of universal quantitative criteria of method development and assessment.A Pd-catalyzed/Cu-mediated oxidative dehydrosulfurative carbon-oxygen cross-coupling reaction of 3,4-dihydropyrimidin-1H-2-thiones (DHPMs) with aryl alcohols is described. Due to the ready availability of diverse DHPMs and aryl alcohols, the reaction method offers facile access to biologically and pharmacologically valuable 2-aryloxypyrimidine derivatives with rapid diversification.Engineering nanoheterostructures (NHs) plays a key role in exploring novel or enhanced physicochemical properties of nanocrystals. Despite previously reported synthetic methodologies, selective synthesis of NHs to achieve the anticipated composition and interface is still challenging. Herein, we presented a colloidal strategy for the regioselective construction of typical Ag-Co2P NHs with precisely controlled location of Ag nanoparticles (NPs) on unique chemically transformed Co2P nanorods (NRs) by simply changing the ratio of different surfactants. As a proof-of-concept study, the constructed heterointerface-dependent hydrogen evolution reaction (HER) catalysis was demonstrated. The multiple Ag NP-tipped Co2P NRs exhibited the best HER performance, due to their more exposed active sites and the synergistic effect at the interfaces. Our results open up new avenues in rational design and fabrication of NHs with delicate control over the spatial distribution and interfaces between different components.Natural products such as conotoxins have tremendous potential as tools for biomedical research and for the treatment of different human diseases. Conotoxins are peptides present in the venoms of predatory cone snails that have a rich diversity of pharmacological functions. One of the major bottlenecks in natural products research is the rapid identification and evaluation of bioactive molecules. To overcome this limitation, we designed a set of light-induced behavioral assays in zebrafish larvae to screen for bioactive conotoxins. We used this screening approach to test several unique conotoxins derived from different cone snail clades and discovered that a conorfamide from Conus episcopatus, CNF-Ep1, had the most dramatic alterations in the locomotor behavior of zebrafish larvae. Interestingly, CNF-Ep1 is also bioactive in several mouse assay systems when tested in vitro and in vivo. Our novel screening platform can thus accelerate the identification of bioactive marine natural products, and the first compound discovered using this assay has intriguing properties that may uncover novel neuronal circuitry.